Randomized Controlled Trial of Intravenous Acetaminophen Versus Intravenous Hydromorphone for the Treatment of Acute Pain in the Emergency Department

Ann Emerg Med. 2019 Feb;73(2):133-140. doi: 10.1016/j.annemergmed.2018.06.019. Epub 2018 Aug 14.


Study objective: As clinicians look to nonnarcotic analgesics in the emergency department (ED), it is essential to understand the effectiveness and adverse effects of nonopioid medications in comparison with existing opioid treatments. Studies of intravenous acetaminophen for acute pain in the ED demonstrate mixed results and suffer from small sample sizes and methodological limitations. This study compares intravenous hydromorphone with intravenous acetaminophen in adult ED patients presenting with acute pain.

Methods: This was a prospective, randomized, clinical trial comparing 1 g intravenous acetaminophen with 1 mg intravenous hydromorphone for treatment of adults with severe, acute pain in the ED. The primary outcome was between-group difference in change in numeric rating scale from baseline to 60 minutes postadministration of study medication. Secondary outcomes included the difference in proportion of patients in each group who declined additional analgesia at 60 minutes, received additional medication before 60 minutes, and developed nausea, vomiting, or pruritus.

Results: Of 220 subjects randomized, 103 patients in each arm had sufficient data for analysis. At 60 minutes, the mean decrease in numeric rating scale pain score was 5.3 in the hydromorphone arm and 3.3 in the acetaminophen arm, a difference of 2.0 (95% confidence interval [CI] 1.2 to 2.7) favoring hydromorphone. A greater proportion of patients in the hydromorphone arm also declined additional analgesia at 60 minutes (65% versus 44%; difference 21%; (95% CI 8% to 35%). There was no difference in the proportion of patients receiving rescue analgesia before 60 minutes. Significantly more subjects in the hydromorphone group developed nausea (19% versus 3%; difference 16%; 95% CI 4% to 28%) and vomiting (14% versus 3%; difference 11%; 95% CI 0% to 23%).

Conclusion: Although both 1 mg intravenous hydromorphone and 1 g intravenous acetaminophen provided clinically meaningful reductions in pain scores, treatment with hydromorphone provided both clinically and statistically greater analgesia than acetaminophen, at the cost of a higher incidence of nausea and vomiting.

Trial registration: ClinicalTrials.gov NCT03107481.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acute Pain / drug therapy*
  • Administration, Intravenous
  • Adult
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Opioid / administration & dosage*
  • Emergency Service, Hospital*
  • Female
  • Humans
  • Hydromorphone / administration & dosage*
  • Male
  • Middle Aged
  • Pain Measurement
  • Prospective Studies
  • Treatment Outcome


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Acetaminophen
  • Hydromorphone

Associated data

  • ClinicalTrials.gov/NCT03107481